Cocktail法研究脉络宁注射液对大鼠CYP1A2、CYP2E1和CYP3A4活性的影响  

Effects of Mailuoning injection on rat activities of CYP1A2,CYP2E1 and CYP3A4 using a three-drug Cocktail approach

作　　者：陈为烤[1] 居文政[2] 许黎君[1] 刘史佳[2] 谈恒山[3] 

机构地区：[1]南京中医药大学 [2]南京中医药大学附属江苏省中医院临床药理科 [3]南京军区总医院临床药理科

出　　处：《中国临床药理学与治疗学》2009年第4期386-390,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：科技部"十一五"支撑计划课题-药物临床研究关键技术研究与应用(2006BAI14B07)

摘　　要：目的:研究脉络宁注射液对大鼠CYP1A2、CYP2E1和CYP3A4活性的影响。方法:14只大鼠随机均分成临床等效剂量组和高剂量组,连续2周静脉给予脉络宁注射液(临床等效剂量组,2 mL/kg;高剂量组,4 mL/kg)前后,均同时灌胃给予3个探针底物(茶碱,30 mg/kg;氯唑沙宗,50 mg/kg;氨苯砜,20 mg/kg),进行采血试验。用HPLC法同时测定大鼠体内各探针的血药浓度,DAS 1.0软件计算药动学参数,并以配对t检验对各组大鼠前后两轮主要药动学参数进行差异性比较。结果:在1个给药疗程(14 d)内,临床等效剂量组大鼠用药前后,3个探针的药动学参数均无显著性变化(P>0.05);高剂量组大鼠用药后,与用药前相比,茶碱的药动学参数没有显著变化(P>0.05);氨苯砜和氯唑沙宗的AUC0-24 h均有升高趋势(P<0.05),给药后分别是给药前的1.44倍和1.28倍,同时氯唑沙宗的CL显著降低(P<0.05)。结论:临床等效剂量脉络宁对大鼠CYP1A2、CYP2E1和CYP3A4活性均无显著影响,而高剂量脉络宁对大鼠CYP2E1和CYP3A4均有弱抑制作用。AIM： To investigate the effects of Mailuoning injection on rat activities of CYP1A2, CYP2E1 and CYP3A4. METHODS： 14 rats were randomly and equally divided into two groups, i.e. clinically- equivalent-dose group and higher-dose group. Two group rats underwent 2-cycle pharmacokinetic experiments before and after being treated with two doses of Mailuoning injection for 14 days, in which the rats were concomitantly administered Theophylline （30 mg/kg）, Chlorzoxazone （50 mg/kg） and Dapsone （20 mg/kg） by gastrogavage, followed by blood-withdrawing from orbital bleeding at different intervals within 24 hours. High-performance liquid chromatography （HPLC） was utilized to simultaneously quantitate 3 probe compounds in rat plasma, and DAS 2.0 Software was used to fit plasma concentration-time curve and calculate their corresponding principal pharmacokinetic parameters, among which the statistical differences were evaluated by Paried t-test. RESULTS： In the 14-day administration period, the 2-cycle pharmaeokinetic parameters of 3 probes for the clinically-equivalent-dose group rats exhibited insignificant differences （P 〉 0.05 ）, meanwhile, after being treated with higher-dose Mailuoning injection, there were no significant differences for theophylline pharmacokinetics in rats, but AUC0- 24 h of dapsone and chlorzoxazone after treatment were 1.27 and 1.44 times larger than those before treatment, respectively and chlorzoxazone CL/F became smaller. CONCLUSION： Clinically-equivalent-dose Mailuoning injection did not affect the activi- ties of rat CYP1A2, CYP2E1 and CYP3A4; higherdose Mailuoning injection could not insignificantly change CYP1A2 activity, but could weakly inhibit activities of CYP2E1 and CYP3A4.

关 键 词：脉络宁注射液 细胞色素P450 茶碱 氯 

分 类 号：R969.1[医药卫生—药理学]